Contribution of Psychological Factors in the Healing of the Diabetic Foot Ulcer

NCT04698720 | Completed

• 1 other identifier: PTCD/PSIGER/ 28163/2017
• Study Type: interventional
• Target: 69
• Locations: 1 country
• Sites: 3

Brief Summary

Diabetic foot ulcers (DFU) are one of the most serious complications of diabetes and can lead to amputations in 85% of cases, resulting in physical, psychological, family, social and economic consequences. Research suggests that psychological factors may play an important role in DFU healing. Relaxation and hypnosis seem to contribute to faster wound healing. More research is needed to assess the effectiveness of different types of intervention on different types of wounds, in particular chronic wounds such as DFU. This study will evaluate the efficacy of relaxation and hypnosis, both with guided imagery, in DFU healing, physiological indicators (inflammatory, metabolic, oxidative stress, angiogenic, and miRNA biomarkers) of wound healing prognosis, and QoL, in patients with diabetic foot and a chronic ulcer. This study is a Randomized Controlled Study of a Psychological Intervention that aims to evaluate the efficiency of a muscle relaxation intervention with guided imagery (experimental group - EG1) compare to a hypnosis intervention with guided imagery (experimental group - EG2) and a neutral guided imagery placebo (active control group - ACG) and a group that does not receive any psychological intervention (passive control group - PCG). This study will also examine, qualitatively, the perspectives of patients with DFU on the relaxation and hypnosis interventions, in order to check its effectiveness; as well as the perspectives of informal caregivers on this adjuvant therapys. Participants must have a diagnosis of Diabetes Mellitus and Diabetic Foot; one or two chronic active ulcers at the time of assessment; and clinical levels of stress or anxiety or depression. Participants will be randomized by the four conditions - EG1, EG2, ACG and PCG - and assessed on the day of the first consultation or nursing treatment for chronic DFU (T0), two months later (T1), and six months later (T2; follow-up). Two weeks after T1, an interview will be conducted independently with patients that completed the relaxation, hypnosis, and placebo sessions, and with the informal caregivers who provided them the DFU care. The results of the present study will contribute for a better understanding of DFU progression, healing, prevention of re-ulceration and future amputations and, consequently, for the improvement of patients' quality of life.

Conditions

Diabetes Mellitus; Diabetic Foot Ulcer

Keywords

Diabetic Foot Ulcer; Ulcer Healing; Quality of Life; Hypnosis; Relaxation

Outcome Measures

Primary Outcomes (9)

• Impact of the DFU on patients' quality of life

  The Diabetic Foot Ulcer Scale-Short Form (DFS-SF; Bann, Fehnel, \& Gagnon, 2003; Research version by Pereira et al., 2022) will be used to assess patients´ DFU-related quality of life. Raw scores are transformed into a scale from 0 to 100. Higher results correspond to better DFU-related quality of life.

  Changes from baseline (T0) to the end of intervention/ 2 months later at post-test (T1), and after 6 months follow-up (T2)

• Degree of DFU healing

  The degree of DFU healing will be assessed with the Portuguese version of "Resultados esperados de la valoración y evolución de la cicatrización de las heridas crónicas" Scale \[Expected results of the evaluation and evolution of the healing of chronic wounds Scale - RESVECH 2.0\] (Marques, 2015). The scores range from 0 to 35, where zero indicates complete healing.

  Changes from baseline (T0) to the end of intervention/ 2 months later at post-test (T1), and after 6 months follow-up (T2)

• Physical quality of life

  The Short-Form Health Survey (SF-36; Ferreira, 1998; Ferreira, Ferreira, \& Pereira, 2012) will be administered to assess patients' physical health-related quality of life. Raw scores are transformed into a scale from 0 to 100. Higher results correspond to better physical quality of life.

  Changes from baseline (T0) to the end of intervention/ 2 months later at post-test (T1), and after 6 months follow-up (T2)

• Mental quality of life

  The Short-Form Health Survey (SF-36; Ferreira, 1998; Ferreira, Ferreira, \& Pereira, 2012) will be administered to assess patients' mental health-related quality of life. Raw scores are transformed into a scale from 0 to 100. Higher results correspond to better mental quality of life.

  Changes from baseline (T0) to the end of intervention/ 2 months later at post-test (T1), and after 6 months follow-up (T2)

• Metabolic marker

  The quantification of HbA1c in the plasma will be performed using the competitive inhibition enzyme immunoassay Cloud Clone Corp

  Changes from baseline (T0) to the end of intervention/ 2 months later at post-test (T1), and after 6 months follow-up (T2)

• Inflammatory markers

  IL-6, IL-8, and TNF-a levels will be evaluated in the plasma using a LEGENDplexTM Human Angiogenesis Panel 1 Mix and Match (9-plex). Blood lymphocyte populations will be assessed in the whole blood by flow cytometry and automated hematological cell counter.

  Changes from baseline (T0) to the end of intervention/ 2 months later at post-test (T1), and after 6 months follow-up (T2)

• Angiogenic markers

  Angiopoietin-2, EGF, FGF-basic, PECAM-1, PIGF, and VEGF levels will be assessed in the plasma using a LEGENDplexTM Human Angiogenesis Panel 1 Mix and Match (9-plex).

  Changes from baseline (T0) to the end of intervention/ 2 months later at post-test (T1), and after 6 months follow-up (T2)

• miRNA markers

  miRNA-21 and miRNA-155 will be assessed with SYBR Green technology, using the RNU6B gene as control.

  Changes from baseline (T0) to the end of intervention/ 2 months later at post-test (T1), and after 6 months follow-up (T2)

• Immune cells

  Blood leukocyte and B and T-cell populations will be assessed in the whole blood by flow cytometry and automated hematological cell counter.

  Changes from baseline (T0) to the end of intervention/ 2 months later at post-test (T1), and after 6 months follow-up (T2)

Secondary Outcomes (5)

• Perceived Stress

  Changes from baseline (T0) to the end of intervention/ 2 months later at post-test (T1), and after 6 months follow-up (T2)

• Emotional Distress

  Changes from baseline (T0) to the end of intervention/ 2 months later at post-test (T1), and after 6 months follow-up (T2)

• Anxiety symptoms

  Changes from baseline (T0) to the end of intervention/ 2 months later at post-test (T1), and after 6 months follow-up (T2)

• Depression symptoms

  Changes from baseline (T0) to the end of intervention/ 2 months later at post-test (T1), and after 6 months follow-up (T2)

• Representations regarding the DFU

  Changes from baseline (T0) to the end of intervention/ 2 months later at post-test (T1), and after 6 months follow-up (T2)

Other Outcomes (6)

• Sociodemographic data

  Baseline (T0)

• Clinical data

  Baseline (T0), end of intervention/ 2 months later at post-test (T1), and after 6 months follow-up (T2)

• Health literacy

  Baseline (T0)

Study Arms (4)

Muscle Relaxation with Guided Imagery

EXPERIMENTAL

Participants in the Experimental Group 1 will receive four individual 45-minute sessions, every two weeks, of progressive muscle relaxation intervention with guided imagery focused on ulcer healing, carried out by the Psychologist responsible for implementing the project, on the day of the Diabetic Foot appointments.

Behavioral: Muscle Relaxation with Guided Imagery

Hypnosis with Guided imagery

EXPERIMENTAL

Participants in the Experimental Group 2 will receive a four individual 45-minute sessions, every two weeks, of hypnosis intervention with guided imagery focused on ulcer healing, carried out by the qualified Hypnotherapists external to the research study, on the day of the Diabetic Foot appointments.

Behavioral: Hypnosis with Guided Imagery

Active Control Group

PLACEBO COMPARATOR

Participants in the ACG will receive four individual 45-minute sessions of neutral guided imagery placebo focused on the patient's life before the foot ulcer, carried out by the Psychologist responsible for implementing the project, on the day of the Diabetic Foot appointments.

Behavioral: Neutral Guided Imagery

Passive Control Group

NO INTERVENTION

Participants in the PCG will not receive any intervention or placebo session.

Interventions

Muscle Relaxation with Guided Imagery BEHAVIORAL

Relaxation intervention session begins with diaphragmatic breathing, followed by Jacobson's progressive muscle relaxation, which involves the contraction and subsequent relaxation of the 16 muscle groups of the body (forearm, arm, upper forehead, eye, mouth, jaw and throat, neck, shoulder, chest, stomach, thigh, leg and foot).The contraction is performed for 7 seconds while the relaxation lasts for about 40 to 50 seconds.The relaxation of the foot muscle group is only performed on the healthy foot, because dressing and bandages may bandage the foot with the DFU, which together with the typical joint stiffness of the diabetic foot, make it difficult to perform. After muscle relaxation, begins the guided imagery focused on DFU healing. The patient is instructed to think about his/her current state of health and to imagine the DFU as a dark area and the healing relaxation as a light associated to pleasant sensations, which will focus on the foot with DFU to heal it.

Muscle Relaxation with Guided Imagery

Hypnosis with Guided Imagery BEHAVIORAL

In the beginning of the first session we apply the Eye-Roll Test for Hypnotizability of Herbert Spiegel. Each session follows the Hypnotic Protocol with the following steps:Pre-talk/Absortion/Ratification/Aliciation/Dissociation/Awakening. The four sessions train the participants in visual, auditory and kinesthetic perception on ulcer healing. The protocol also promotes medical treatment acceptance.

Hypnosis with Guided imagery

Neutral Guided Imagery BEHAVIORAL

This placebo consists of neutral guided imagery focused on themes of the patient's daily life before having DFU. Each session has a theme associated with the patient's life - family, work, friends, and leisure. Initially, the patient is asked to think about an event related to the theme of the session of his/her choice, positive or negative, which occurred before patient has the current DFU. Then, the patient is asked about a number of questions regarding the chosen episode in order to promote a more detailed reconstruction of the event. The patient is asked to imagine according to the instructions given by the Psychologist. When the whole episode is remembered, the patient is asked to tell what he or she imagined/remembered regarding each of the questions.

Active Control Group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• years old or older;
• Diabetes Mellitus diagnosis;
• Diagnosis of Diabetic Foot;
• Having one or two active chronic ulcers (\> 6 weeks and \< 14 weeks) at the time of baseline assessment;
• Being followed at the Multidisciplinary Consultation of the Diabetic Foot from the Centro Hospitalar Universitário do Porto (CHUP), at the Diabetic Foot Clinic from the Centro Hospitalar do Tâmega e Sousa (CHTS) and from the Multidisciplinary Consultation of the Diabetic Foot of the Hospital de Braga (HB);
• Presenting clinical levels of stress (scores \> 13 for males and \> 17 for females on the Perceived Stress Scale) or anxiety or depression (scores \> 11 on Hospital Anxiety and Depression Scale);
• Providing written informed consent.

You may not qualify if:

• The active DFU at the time of the assessment being a relapse;
• Having more than two DFUs at the time of baseline assessment;
• Being on hemodialysis treatment;
• Presence of psychosis or dementia described in the patient's medical record;
• Having cancer disease;
• Having undergone a transplant;
• Receiving psychological counselling at the time of the assessment.
• For the RCT qualitative nested study, twelve participants that completed at least 75% of the treatment or placebo sessions, and that report having a informal/ family caregiver will be invite the participate. Participants will be selected according to the following criteria:
• Two typical cases of successful and unsuccessful patients with neuropathic foot, defined by the presence of neuropathic pain (e.g., heat, tingling, electrical shock), presence of distal pulses by palpation, and loss of protective sensitivity;
• Two typical cases of successful and unsuccessful patients with neuroischemic foot, defined by the presence of peripheral artery disease, intense-variable pain, absence of distal pulses by palpation, and variable protective sensitivity.

Sponsors & Collaborators

• University of Minho: lead
• Foundation for Science and Technology, Portugal: collaborator

Study Sites (3)

Hospital de Braga

Braga, 4710-243, Portugal

Location

Clínica do Pé Diabético, Centro Hospitalar do Tâmega e Sousa

Penafiel, 4564-007, Portugal

Location

Centro Hospitalar Universitário do Porto

Porto, 4099-001, Portugal

Location

Related Publications (17)

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• Direção-Geral de Saúde, DGS [General Health Direction, Portugal] Circular Normativa Nº:05/PNPCD: Pé Diabético, Programa Nacional de Prevenção e Controlo da Diabetes (PNPCD) [Normative Circular Nº: 05 / PNPCD: Diabetic Foot, National Diabetes Prevention and Control Program]; 2010. Retrieved from http://www.dgs.pt/?cr=15718

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• Ferreira P. A medição do estado de saúde: Criação da versão portuguesa do MOS SF-36 [Measuring health status: Creation of the Portuguese version of MOS SF-36]. Coimbra: Centro de Estudos e Investigação em Saúde, Faculdade de Economia, Universidade de Coimbra; 1998. Ferreira PL, Ferreira LN, Pereira LN. Medidas sumário física e mental de estado de saúde para a população portuguesa [Physical and mental summary measures of health state for the Portuguese population]. Revista Portuguesa de Saúde Pública. 2012;30(2):163-171. doi:10.1016/j.rpsp.2012.12.007.

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• Figueiras M, Marcelino DS, Claudino A, Cortes MA, Maroco J, Weinman J. Patients' illness schemata of hypertension: the role of beliefs for the choice of treatment. Psychol Health. 2010 Apr;25(4):507-17. doi: 10.1080/08870440802578961.

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  PMID: 30060763 BACKGROUND

• International Working Group on the Diabetic Foot [IWGDF] International Consensus on the Diabetic Foot. International Diabetes Foundation; 2015. Retrieved from http://www.iwgdf.org/files/2015/website_prevention.pdf

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• Marques JM. Adaptação cultural e validação para a população portuguesa de um instrumento de monitorização de feridas crónicas - escala RESVECH 2.0 [Cultural adaptation and validation for the Portuguese population of a chronic wound monitoring instrument - RESVECH 2.0 scale] (Master's Thesis). Instituto de Ciências da Saúde da Universidade Católica, Porto; 2015.

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• Ferreira G, Faria S, Carvalho A, Pereira MG. Relaxation intervention to improve diabetic foot ulcer healing: Results from a pilot randomized controlled study. Wound Repair Regen. 2023 Jul-Aug;31(4):528-541. doi: 10.1111/wrr.13085. Epub 2023 May 9.

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MeSH Terms

Conditions

Diabetes Mellitus; Diabetic Foot

Interventions

Muscle Relaxation; Imagery, Psychotherapy; Hypnosis

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Diabetic Angiopathies; Vascular Diseases; Cardiovascular Diseases; Foot Ulcer; Leg Ulcer; Skin Ulcer; Skin Diseases; Skin and Connective Tissue Diseases; Diabetes Complications; Diabetic Neuropathies

Intervention Hierarchy (Ancestors)

Muscle Contraction; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena; Mind-Body Therapies; Complementary Therapies; Therapeutics; Psychotherapy; Behavioral Disciplines and Activities

Study Officials

• M. Graça Pereira, PhD

  School of Psychology, University of Minho

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Masking Details: Double (Participant, Outcomes Assessor) Eligible participants will be randomized into the four groups into blocks of variable size, multiples of three; and will be stratified according to: i) data collection site; ii) Chronic Renal Disease (CRD); and iii) Peripheral Arterial Disease (PAD); since CRD and PAD are factors of poor prognosis in the DFU healing (Ferreira et al., 2014). This procedure will be performed using an online random number generator by an independent researcher unaware of the numeric coding for each group. After this procedure, it will not be possible to conceal the group to which the patient belongs from the researcher that will perform the psychological and placebo interventions. However, health professionals will be blinded during the entire procedure as they will only fill in the clinical questionnaire (doctors) and the RESVECH 2.0 (nurses), which assesses the DFU healing.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor with Aggregation of School of Psychology

Model Details: Parallel Assignment This is a Randomized Controlled Study of a Psychological Intervention (Grant et al., 2018). This study will use a mixed-methods approach nested in a 4-arm randomized control design. Qualitative and quantitative data will be collected in order to provide better understanding about the effectiveness of the hypnosis intervention in patients with DFU. Participants will be randomised at a ratio of 1:1 for the four conditions - EG1, EG2, ACG and PCG; and will be evaluated on the day of the first chronic DFU appointment or nursing treatment (T0), two months later (at the end of the intervention in EG, EG2, and ACG; T1), as well as six months later (T2) in a follow-up evaluation. Participants from all four groups will undergo standard treatment for the DFU, according to the guidelines of the Portuguese General Health Direction (DGS, 2010) and the International Working Group on the Diabetic Foot (IWGDF, 2015).

Study Record Dates

• First Submitted: December 30, 2020
• First Posted: January 7, 2021
• Study Start: February 1, 2019
• Primary Completion: December 31, 2021
• Study Completion: July 25, 2022
• Last Updated: May 8, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

PT (3)